Experimental systems for studying the role of G-protein-coupled receptors in receptor tyrosine kinase signal transduction

Nigel J Pyne, Catherine Waters, Noreen Akhtar Moughal, Balwinder Sambi, Michelle Connell, Susan Pyne

Research output: Contribution to journalSpecial issuepeer-review

8 Citations (Scopus)


Early conception of G-protein-coupled receptor (GPCR) and receptor tyrosine kinase (RTK) signaling pathways was that each represented distinct and linear modules that converged on downstream targets, such as p42/p44 mitogen-activated protein kinase (MAPK). It has now become clear that this is not the case and that multiple levels of cross-talk exist between both receptor systems at early points during signaling events. In recent years, it has become apparent that transactivation of receptor tyrosine kinases by GPCR agonists is a general phenomenon that has been demonstrated for many unrelated GPCRs and receptor tyrosine kinases. In this case, GPCR/G-protein participation is upstream of the receptor tyrosine kinase. However, evidence now demonstrates that numerous growth factors use G proteins and associated signaling molecules such as beta-arrestins that participate downstream of the receptor tyrosine kinase to signal to effectors, such as p42/p44 MAPK. This article highlights experimental approaches used to investigate this novel mechanism of cross-talk between receptor tyrosine kinases and GPCRs.
Original languageEnglish
Pages (from-to)451-475
Number of pages25
JournalMethods in Enzmology
Early online date18 Oct 2004
Publication statusPublished - 2004


  • animals
  • arrestins
  • cell line
  • humans
  • mitogen-activated protein kinases
  • pertussis toxin
  • phosphorylation
  • receptor protein-tyrosine Kinases
  • receptor, nerve growth factor
  • receptor, platelet-derived Growth Factor beta
  • receptors, G-protein-coupled
  • receptors, lysosphingolipid
  • signal transduction
  • tyrosine
  • tyrphostins


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